Skip to main content

Advertisement

Log in

The Effect of Stromal Cell-Derived Factor 1 in the Migration of Neural Stem Cells

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

Neural stem cells (NSCs) have widely been used in the treatment of human neurological disorders as cell therapy via intracerebral or intraventricular infusion. However, the migration mechanism required for NSCs homing and recruitment remains to be elucidated. Recently, SDF-1/CXCR4 axis was shown to be responsible for in cell migration and differentiation during the neural development stage and involved in the pathophysiological process of neurological disorders. In this study, we investigated the effect of SDF-1 in migration of NSCs in vitro and in vivo. The expression of CXCR4 receptor was examined by immunocytochemistry and RT-PCR. The migratory ability of NSCs induced by SDF-1 was assessed by transwell chemotaxis assay. The traumatic brain injury rat model was well established, and the recruitment of NSCs and expression of SDF-1 were investigated in vivo. Our findings demonstrated that SDF-1, in vitro, significantly induced the migratory of NSCs in a dose-dependent manner. An overexpression of neural stem cell marker Nestin in the hippocampus was observed after TBI, and the expressions of SDF-1 surrounding the lesion areas were significantly increased. Our results suggested that the migration of NSCs was activated by chemotactic effect of SDF-1. It was also proved the relevance of SDF-1 in the migration of endogenous NSCs after brain injury. Taken together, these results demonstrated that SDF-1/CXCR4 axis may play crucial role in the migration of Nestin-positive cell after brain injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Noda, M., et al. (2011). CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice. Blood, 117(2), 451–458.

    Article  CAS  PubMed  Google Scholar 

  2. Li, M., et al. (2011). Chemokine receptor CXCR4 signaling modulates the growth factor-induced cell cycle of self-renewing and multipotent neural progenitor cells. Glia, 59(1), 108–118.

    Article  PubMed  Google Scholar 

  3. Huber, B. C., et al. (2011). Parathyroid hormone is a DPP-IV inhibitor and increases SDF-1-driven homing of CXCR4(+) stem cells into the ischaemic heart. Cardiovascular Research, 90(3), 529–537.

    Article  CAS  PubMed  Google Scholar 

  4. Bellmann-Sickert, K., & Beck-Sickinger, A. G. (2011). Palmitoylated SDF1 alpha shows increased resistance against proteolytic degradation in liver homogenates. ChemMedChem, 6(1), 193–200.

    Article  CAS  PubMed  Google Scholar 

  5. Zou, L. P., et al. (2011). Expression of SDF-1 in lung tissues and intervention of AMD3100 in asthmatic rats. Zhongguo Dang Dai Er Ke Za Zhi, 13(4), 321–325.

    CAS  PubMed  Google Scholar 

  6. Janssen, U., et al. (2002). Differential expression of MCP-1 and its receptor CCR2 in glucose primed human mesangial cells. Nephron, 92(4), 797–806.

    Article  CAS  PubMed  Google Scholar 

  7. Ma, Q., et al. (1998). Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 95(16), 9448–9453.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Gouwy, M., et al. (2011). CXCR4 and CCR5 ligands cooperate in monocyte and lymphocyte migration and in inhibition of dual-tropic (R5/X4) HIV-1 infection. European Journal of Immunology, 41(4), 963–973.

    Article  CAS  PubMed  Google Scholar 

  9. Gassmann, P., et al. (2009). CXCR4 regulates the early extravasation of metastatic tumor cells in vivo. Neoplasia, 11(7), 651–661.

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Egawa, T., et al. (2001). The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity, 15(2), 323–334.

    Article  CAS  PubMed  Google Scholar 

  11. Levesque, J. P., et al. (2003). Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. Journal of Clinical Investigation, 111(2), 187–196.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Yang, S., et al. (2013). Cxcl12/Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons. Development, 140(22), 4554–4564.

    Article  CAS  PubMed  Google Scholar 

  13. Aiuti, A., et al. (1997). The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. Journal of Experimental Medicine, 185(1), 111–120.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Werner, L., Guzner-Gur, H., & Dotan, I. (2013). Involvement of CXCR4/CXCR7/CXCL12 interactions in inflammatory bowel disease. Theranostics, 3(1), 40–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Comerford, I., et al. (2012). PI3K gamma drives priming and survival of autoreactive CD4(+) T cells during experimental autoimmune encephalomyelitis. PLoS ONE, 7(9), e45095.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Karin, N. (2010). The multiple faces of CXCL12 (SDF-1 alpha) in the regulation of immunity during health and disease. Journal of Leukocyte Biology, 88(3), 463–473.

    Article  CAS  PubMed  Google Scholar 

  17. Imitola, J., et al. (2004). Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1 alpha/CXC chemokine receptor 4 pathway. Proceedings of the National Academy of Sciences of the United States of America, 101(52), 18117–18122.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Kucia, M., et al. (2004). Cells expressing early cardiac markers reside in the bone marrow and are mobilized into the peripheral blood after myocardial infarction. Circulation Research, 95(12), 1191–1199.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Vasyutina, E., et al. (2005). CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Genes & Development, 19(18), 2187–2198.

    Article  CAS  Google Scholar 

  20. Nelson, R. D., & Herron, M. J. (1988). Agarose method for human neutrophil chemotaxis. Methods in Enzymology, 162, 50–59.

    Article  CAS  PubMed  Google Scholar 

  21. Malkesman, O., et al. (2013). Traumatic brain injury—Modeling neuropsychiatric symptoms in rodents. Frontiers in Neurology, 4, 157.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Weber, J. T. (2007). Experimental models of repetitive brain injuries. Progress in Brain Research, 161, 253–261.

    Article  PubMed  Google Scholar 

  23. Petchprapai, N., & Winkelman, C. (2007). Mild traumatic brain injury: Determinants and subsequent quality of life. A review of the literature. Journal of Neuroscience Nursing, 39(5), 260–272.

    Article  PubMed  Google Scholar 

  24. Fricker, S. P., et al. (2006). Characterization of the molecular pharmacology of AMD3100: A specific antagonist of the G-protein coupled chemokine receptor, CXCR4. Biochemical Pharmacology, 72(5), 588–596.

    Article  CAS  PubMed  Google Scholar 

  25. Peng, H., et al. (2007). Differential expression of CXCL12 and CXCR4 during human fetal neural progenitor cell differentiation. Journal of Neuroimmune Pharmacology, 2(3), 251–258.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Marquez-Curtis, L. A., & Janowska-Wieczorek, A. (2013). Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 Axis. Biomed Research International, 2013, 561098.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kucia, M., et al. (2004). Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury. Blood Cells, Molecules, & Diseases, 32(1), 52–57.

    Article  CAS  Google Scholar 

  28. Heit, B. and P. Kubes, Measuring chemotaxis and chemokinesis: the under-agarose cell migration assay. Sci STKE, 2003. 2003(170): p. PL5.

  29. Woznica, D., & Knecht, D. A. (2006). Under-agarose chemotaxis of Dictyostelium discoideum. Methods in Molecular Biology, 346, 311–325.

    CAS  PubMed  Google Scholar 

  30. Durbec, P., et al. (2008). In vitro migration assays of neural stem cells. Methods in Molecular Biology, 438, 213–225.

    Article  CAS  PubMed  Google Scholar 

  31. Wong, K., et al. (2008). Assessing neural stem cell motility using an agarose gel-based microfluidic device. Journal of visualized experiments 12.

  32. Zhang, J., et al. (2013). The small molecule Me6TREN mobilizes hematopoietic stem/progenitor cells by activating MMP-9 expression and disrupting SDF-1/CXCR4 axis. Blood.

  33. Lapidot, T., & Kollet, O. (2002). The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2 m(null) mice. Leukemia, 16(10), 1992–2003.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a special Grant for High-Level Training of Yun Nan (2013FZ280) and a special joint grant of Yunnan Provincial Science and Technology Department and Kunming Medical University (2010CD157). This work is supported by special training funding (No. 2013FZ280) for high-level experts of Yunnan Province, and Joint program (No. 2010CD157) of Department of technology, Yunnan province and Yunnan Medical University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peng Ding.

Additional information

Liping Xue and Jinkun Wang have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xue, L., Wang, J., Wang, W. et al. The Effect of Stromal Cell-Derived Factor 1 in the Migration of Neural Stem Cells. Cell Biochem Biophys 70, 1609–1616 (2014). https://doi.org/10.1007/s12013-014-0103-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0103-5

Keywords

Navigation